DESCRIPTION: The past decade has seen rapid changes in the use of cisplatin-based chemotherapy in head and neck cancers. Previously untreated patients have partial response rates to cisplatin of 70-90 percent. However, in the relapse setting, these rates are much lower, with only about one-third responding. Since cisplatin-based chemotherapy is expensive and toxic, it would be extremely useful to be able to predict which patients are likely to respond to cisplatin and which are not. The applicant's preliminary data show a striking correlation of glutathione S-transferase (GST) expression in head and neck tumor biopsies with response to cisplatin-based therapy. There is also a remarkably linear correlation of GSH content in head and neck cell lines with cisplatin toxicity. Based on the applicant's preliminary data, the fundamental hypothesis is that measurement of enzymes in the glutathione pathway will predict response to cisplatin-based chemotherapy in head and neck cancer. To test this hypothesis, the applicant proposes the following specific aims: (1) to quantify expression of glutathione S-transferase, gamma-glutamylcysteine synthetase, glutathione synthetase, glutathione transpeptidase and multidrug resistance-associated protein (MRP) in clinical head and neck biopsy specimens, and correlate expression with chemotherapy response, site, stage and clinical outcome; (2) to quantify the expression of related proteins which may also impact on chemotherapy response and survival in head and neck cancer, thymidylate synthase, p53 and erbB-2 and to correlate expression of these with chemotherapy response, site, stage and clinical outcome; (3) to statistically determine the optimum combination of measurements described above to produce an accurate and reproducible prediction of chemotherapy response and prognosis; and (4) to validate a quantitative flow cytometric method for measuring glutathione directly in needle aspirates and needle biopsies of head and neck tumors.